The incidence of melanoma has been increasing steadily in both men and women for more than a decade. It is currently the fifth leading cause of cancer in men and the seventh in women. Immunotherapy using high-dose intravenous interleukin-2 (HD IL-2) has demonstrated modest response rates (˜16%) in patients with metastatic disease, but many who undergo complete response will have durable responses beyond 10 years. HD IL-2 in combination with infusion of tumor-infiltrating lymphocytes (TILs) has increased the objective response rate to as high as 72% and durable complete response in up to 16% of patients with metastatic melanoma. These studies demonstrate proof-of-concept that immunotherapy can be efficacious in selected patients. However, there are significant limitations related to IL-2 toxicity and challenges surrounding the isolation and expansion of TILs in vitro that have limited the translation of this approach outside of a relatively few investigational sites. In addition, because many patients with stage III melanoma do not have significant volumes of tumor, TIL therapy is not feasible in this patient population.